Impact of age on modulation of norepinephrine release from sympathetic nerves in the rat superior mesentery artery.
There is an age-related increase in stimulation-evoked fractional norepinephrine release in tail arteries of Fischer 344 rats from 6-20 months of age. Previous studies have ruled out changes in the function of uptake and subsequent metabolism mechanisms, or feedback by prejunctional alpha2-adrenoceptors. The tail artery is important in thermoregulation, and there is the possibility that the previously observed increase in sympathetic nerve activity is due to age-related changes in thermoregulation as opposed to a fundamental age-related change in the regulation of sympathetic nerves. Thus, we measured stimulation-evoked norepinephrine release in another blood vessel model, the superior mesentery artery using HPLC with electrochemical detection. In this study fractional norepinephrine release was measured under three separate conditions, drug free Krebs'; in the presence of deoxycorticosterone and cocaine; in the presence of deoxycorticosterone and cocaine and the alpha2-adrenergic receptor antagonist, idazoxan. The most significant finding was that fractional norepinephrine release in mesentery arteries from 20-month-old animals was higher as compared to 6 months regardless of treatment condition. Furthermore, the elevation in norepinephrine release cannot be accounted for by changes in norepinephrine content, uptake and subsequent metabolism mechanisms or changes in basal norepinephrine release. These data from the mesentery artery model confirm and support our previous work in the rat tail artery model. In addition, the data from this study suggest the possibility that there are common mechanisms underlying the age-related increase in peripheral sympathetic nerve activity.
Buchholz
J
J
Department of Pharmacology, School of Medicine, Loma Linda University, CA 92350, USA. jbuchholz@ccmail.llu.edu
Sexton
P
P
Hewitt
C W
CW
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004558:Electric Stimulation; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D003900:Desoxycorticosterone; D003042:Cocaine; D009638:Norepinephrine; D019329:Idazoxan